The core of this 'Resource' is a novel type of secondary ion mass spectrometer, the Multi-Isotope Imaging Mass Spectrometer (MIMS). Secondary ion mass spectrometry is based upon the sputtering of a few atomic layers from the surface of a sample. During the ejection process, some atoms and clusters are spontaneously ionized. These 'secondary ions' are a characteristic of the composition of the analyzed surface. The secondary ions are separated according to their mass, and an image containing quantitative information can be formed for a selected mass. MIMS provides a high mass separation (M/DM > 10,000), a high spatial resolution (< 50 nm) and has the unique capability of recording simultaneously several atomic mass images. Of the utmost importance, MIMS makes possible for the first time (and at the intracellular level) to simultaneously image the distribution and measure the accumulation of molecules labeled with any isotopes, in particular with stable isotopes, for example with 15N and/or 13C, Deuterium, 18O, or 17O. Multiple labeling can be used on different or on the same molecules. Thus, MIMS allows one to study the localization, the accumulation and the turnover of proteins, fats, sugars and foreign molecules in cellular microdomains. The Resource collaborates with and serves researchers to develop methods for using the unique advantages of MIMS to bring original information in cell biology, physiology, physiopathology, biochemistry, immunology, transplantation pharmacology, toxicology, stem cell and gone transfer research. MIMS offers a powerful and quantitative new method for studying intra and transcellular metabolic pathways, signal transduction, cytoplasmic and nucleo-cytoplasmic translocation, RNA and DNA expression and distribution, fatty acid transport, donor-receiver cellular trafficking and localization of drugs. Instrumental development (brighter Cesium primary ion source, iodine negative primary ion source, impregnation by 'soft landing' of the primary atoms) will increase the resolution down to 20nm, will allow sensitive measurements of calcium, alkali metals (Na, K), metals (metalloenzymes) and will allow analysis of the very first atomic layers at the cell surface. A workshop will be organized at least every other year to train users. Each year, a resource 'booth' will disseminate the resource activities at one major national meeting (FASEB, Cell Biology). Training and dissemination will also be facilitated because, for MIMS analysis, researchers can develop preparative methods starting from procedures well established for the observation of tissues and/or cells. All the Resource activities are greatly benefiting from the enthusiastic participation of the Physicist who originated the MIMS and of the highly expert engineer who directed the making of the instrument. Finally, the use of stable isotopes opens a world of labeling possibilities that were impossible with auto-radiography. It opens the possibility to broadly expand the use of tracers in humans for diagnosis and clinical research purposes.